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  1. Article ; Online: Resolved: EMT Produces Fibroblasts in the Kidney.

    Zeisberg, Michael

    Journal of the American Society of Nephrology : JASN

    2023  Volume 21, Issue 8, Page(s) 1247–1253

    Language English
    Publishing date 2023-03-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/01.asn.0000926916.36548.91
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  2. Book ; Thesis: Die Bedeutung des Basic Fibrolast Growth Factors bei der renalen Fibrogenese

    Zeisberg, Michael

    2000  

    Author's details vorgelegt von Michael Zeisberg
    Language German
    Size 93 Bl. : Ill., graph. Darst.
    Edition [Mikrofiche-Ausg.]
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Göttingen, Univ., Diss., 2001
    HBZ-ID HT013405835
    Database Catalogue ZB MED Medicine, Health

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  3. Article: Precision renal medicine: a roadmap towards targeted kidney fibrosis therapies.

    Zeisberg, Michael / Zeisberg, Elisabeth M

    Fibrogenesis & tissue repair

    2015  Volume 8, Page(s) 16

    Abstract: Based on extensive pre-clinical achievements over the past decades, it appears to be due time for a successful clinical translation in the renal fibrosis field-but what is the quickest road to get there? In light of the recent launch of the Precision ... ...

    Abstract Based on extensive pre-clinical achievements over the past decades, it appears to be due time for a successful clinical translation in the renal fibrosis field-but what is the quickest road to get there? In light of the recent launch of the Precision Medicine Initiative and success of molecularly informed drugs in oncology, we here discuss what it may take to bring molecularly targeted anti-fibrotic to clinical use in chronic progressive kidney disease.
    Language English
    Publishing date 2015-09-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2460211-5
    ISSN 1755-1536
    ISSN 1755-1536
    DOI 10.1186/s13069-015-0033-x
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  4. Article ; Online: Evidence for antifibrotic incretin-independent effects of the DPP-4 inhibitor linagliptin.

    Zeisberg, Michael / Zeisberg, Elisabeth M

    Kidney international

    2015  Volume 88, Issue 3, Page(s) 429–431

    Abstract: Among gliptins, linagliptin is unique, because decreased glomerular filtration rate does not require dose reduction. Linagliptin was originally developed to lower blood glucose by inhibiting dipeptidyl peptidase-4 (DPP-4). However, DPP-4 has numerous ... ...

    Abstract Among gliptins, linagliptin is unique, because decreased glomerular filtration rate does not require dose reduction. Linagliptin was originally developed to lower blood glucose by inhibiting dipeptidyl peptidase-4 (DPP-4). However, DPP-4 has numerous additional substrates, and thus gliptins possess a vast range of additional off-target effects. Shi et al. report that linagliptin directly targets interaction of DPP-4 with integrin β1, preventing endothelial-mesenchymal transition and ultimately renal fibrosis, providing additional rationale for use of linagliptin in diabetic nephropathy.
    MeSH term(s) Animals ; Diabetes Mellitus, Experimental/enzymology ; Diabetic Nephropathies/enzymology ; Dipeptidyl Peptidase 4/metabolism ; Endothelial Cells/enzymology ; Epithelial-Mesenchymal Transition ; Integrin beta1/metabolism ; Kidney/enzymology ; Male
    Chemical Substances Integrin beta1 ; Dipeptidyl Peptidase 4 (EC 3.4.14.5)
    Language English
    Publishing date 2015-09
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1038/ki.2015.175
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    Zs.A 797: Show issues Location:
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  5. Article ; Online: Chromatin dynamics at the core of kidney fibrosis.

    Tampe, Björn / Zeisberg, Michael

    Matrix biology : journal of the International Society for Matrix Biology

    2018  Volume 68-69, Page(s) 194–229

    Abstract: Progression of chronic kidney disease is a principal challenge in Nephrology, as effective therapies to halt or even reverse established lesion are not available yet. While numerous growth factors and environmental stimuli that drive progression of ... ...

    Abstract Progression of chronic kidney disease is a principal challenge in Nephrology, as effective therapies to halt or even reverse established lesion are not available yet. While numerous growth factors and environmental stimuli that drive progression of chronic kidney disease are present within the fibrotic microenvironment, the effector cells' genetic information needs to be accessible in order to enable the pro-fibrotic response. As more than 2 m of DNA encoding the genetic information is crammed as protein-DNA complex called chromatin within the nucleus of each cell, an accessible chromatin state is a prerequisite in the hierarchical order of events to enable production of fibrotic proteins and fibrotic cellular responses. Here, we review contribution and underlying mechanisms of chromatin organization, histone modifications and DNA methylation to progression of chronic kidney disease, provide recent evidence for cell type-specific cell fate decisions and discuss possible diagnostic and therapeutic applications.
    MeSH term(s) Chromatin/genetics ; Chromatin Assembly and Disassembly ; DNA Methylation ; Disease Progression ; Epigenesis, Genetic ; Fibrosis ; Histone Code ; Humans ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/pathology
    Chemical Substances Chromatin
    Language English
    Publishing date 2018-02-21
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1183793-7
    ISSN 1569-1802 ; 0945-053X
    ISSN (online) 1569-1802
    ISSN 0945-053X
    DOI 10.1016/j.matbio.2018.02.015
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  6. Article ; Online: Low levels of circulating methylated IRX3 are related to worse outcome after transcatheter aortic valve implantation in patients with severe aortic stenosis.

    Kanwischer, Leon / Xu, Xingbo / Saifuddin, Afifa Binta / Maamari, Sabine / Tan, Xiaoying / Alnour, Fouzi / Tampe, Björn / Meyer, Thomas / Zeisberg, Michael / Hasenfuss, Gerd / Puls, Miriam / Zeisberg, Elisabeth M

    Clinical epigenetics

    2023  Volume 15, Issue 1, Page(s) 149

    Abstract: Background: Aortic stenosis (AS) is one of the most common cardiac diseases and major cause of morbidity and mortality in the elderly. Transcatheter aortic valve implantation (TAVI) is performed in such patients with symptomatic severe AS and reduces ... ...

    Abstract Background: Aortic stenosis (AS) is one of the most common cardiac diseases and major cause of morbidity and mortality in the elderly. Transcatheter aortic valve implantation (TAVI) is performed in such patients with symptomatic severe AS and reduces mortality for the majority of these patients. However, a significant percentage dies within the first two years after TAVI, such that there is an interest to identify parameters, which predict outcome and could guide pre-TAVI patient selection. High levels of cardiac fibrosis have been identified as such independent predictor of cardiovascular mortality after TAVI. Promoter hypermethylation commonly leads to gene downregulation, and the Iroquois homeobox 3 (IRX3) gene was identified in a genome-wide transcriptome and methylome to be hypermethylated and downregulated in AS patients. In a well-described cohort of 100 TAVI patients in which cardiac fibrosis levels were quantified histologically in cardiac biopsies, and which had a follow-up of up to two years, we investigated if circulating methylated DNA of IRX3 in the peripheral blood is associated with cardiac fibrosis and/or mortality in AS patients undergoing TAVI and thus could serve as a biomarker to add information on outcome after TAVI.
    Results: Patients with high levels of methylation in circulating IRX3 show a significantly increased survival as compared to patients with low levels of IRX3 methylation indicating that high peripheral IRX3 methylation is associated with an improved outcome. In the multivariable setting, peripheral IRX3 methylation acts as an independent predictor of all-cause mortality. While there is no significant correlation of levels of IRX3 methylation with cardiac death, there is a significant but very weak inverse correlation between circulating IRX3 promoter methylation level and the amount of cardiac fibrosis. Higher levels of peripheral IRX3 methylation further correlated with decreased cardiac IRX3 expression and vice versa.
    Conclusions: High levels of IRX3 methylation in the blood of AS patients at the time of TAVI are associated with better overall survival after TAVI and at least partially reflect myocardial IRX3 expression. Circulating methylated IRX3 might aid as a potential biomarker to help guide both pre-TAVI patient selection and post-TAVI monitoring.
    MeSH term(s) Humans ; Aortic Valve Stenosis/genetics ; Aortic Valve Stenosis/surgery ; Biopsy ; Cell-Free Nucleic Acids ; DNA Methylation ; Homeodomain Proteins/genetics ; Transcatheter Aortic Valve Replacement/adverse effects ; Transcription Factors/genetics
    Chemical Substances Cell-Free Nucleic Acids ; Homeodomain Proteins ; IRX3 protein, human ; Transcription Factors
    Language English
    Publishing date 2023-09-11
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553921-8
    ISSN 1868-7083 ; 1868-7075
    ISSN (online) 1868-7083
    ISSN 1868-7075
    DOI 10.1186/s13148-023-01561-2
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  7. Article ; Online: CRISPR/Cas Derivatives as Novel Gene Modulating Tools: Possibilities and In Vivo Applications.

    Xu, Xingbo / Hulshoff, Melanie S / Tan, Xiaoying / Zeisberg, Michael / Zeisberg, Elisabeth M

    International journal of molecular sciences

    2020  Volume 21, Issue 9

    Abstract: The field of genome editing started with the discovery of meganucleases (e.g., the LAGLIDADG family of homing endonucleases) in yeast. After the discovery of transcription activator-like effector nucleases and zinc finger nucleases, the recently ... ...

    Abstract The field of genome editing started with the discovery of meganucleases (e.g., the LAGLIDADG family of homing endonucleases) in yeast. After the discovery of transcription activator-like effector nucleases and zinc finger nucleases, the recently discovered clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated proteins (Cas) system has opened a new window of applications in the field of gene editing. Here, we review different Cas proteins and their corresponding features including advantages and disadvantages, and we provide an overview of the different endonuclease-deficient Cas protein (dCas) derivatives. These dCas derivatives consist of an endonuclease-deficient Cas9 which can be fused to different effector domains to perform distinct in vitro applications such as tracking, transcriptional activation and repression, as well as base editing. Finally, we review the in vivo applications of these dCas derivatives and discuss their potential to perform gene activation and repression in vivo, as well as their potential future use in human therapy.
    MeSH term(s) Bacterial Proteins/metabolism ; CRISPR-Associated Protein 9/metabolism ; CRISPR-Cas Systems ; Chromatin/ultrastructure ; DNA/metabolism ; Endodeoxyribonucleases/metabolism ; Endonucleases/metabolism ; Epigenomics/methods ; Gene Editing/methods ; Gene Transfer Techniques ; Green Fluorescent Proteins/analysis ; Green Fluorescent Proteins/genetics ; Optical Imaging ; RNA, Guide, CRISPR-Cas Systems/genetics ; Recombinant Fusion Proteins/analysis ; Substrate Specificity ; Telomere/ultrastructure ; Transcription Activator-Like Effector Nucleases/metabolism ; Transcription Activator-Like Effectors/metabolism ; Transcription, Genetic ; Zinc Fingers
    Chemical Substances Bacterial Proteins ; Chromatin ; RNA, Guide, CRISPR-Cas Systems ; Recombinant Fusion Proteins ; Transcription Activator-Like Effectors ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9) ; DNA (9007-49-2) ; CRISPR-Associated Protein 9 (EC 3.1.-) ; Cas12a protein (EC 3.1.-) ; Endodeoxyribonucleases (EC 3.1.-) ; Endonucleases (EC 3.1.-) ; Transcription Activator-Like Effector Nucleases (EC 3.1.-)
    Language English
    Publishing date 2020-04-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21093038
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  8. Article ; Online: ANCA vasculitis meets epigenetics--closing in on the molecular roots of disease.

    Zeisberg, Michael

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2011  Volume 26, Issue 4, Page(s) 1146–1148

    MeSH term(s) Animals ; Antibodies, Antineutrophil Cytoplasmic/genetics ; Antibodies, Antineutrophil Cytoplasmic/immunology ; Epigenomics ; Humans ; Vasculitis/genetics ; Vasculitis/immunology
    Chemical Substances Antibodies, Antineutrophil Cytoplasmic
    Language English
    Publishing date 2011-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfq834
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  9. Book ; Online ; Thesis: Untersuchung der pharmakologischen Modulation von ARNT-Homodimeren auf die Renoprotektion

    Rapp, Gregor Christof [Verfasser] / Zeisberg, Michael [Akademischer Betreuer] / Neeße, Albrecht Prof [Gutachter] / Schön, Margarete [Gutachter]

    2023  

    Author's details Gregor Christof Rapp ; Gutachter: Albrecht Prof Neeße, Margarete Schön ; Betreuer: Michael Zeisberg
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language German
    Publisher Niedersächsische Staats- und Universitätsbibliothek Göttingen
    Publishing place Göttingen
    Document type Book ; Online ; Thesis
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  10. Article ; Online: PP2A phosphatase inhibition is anti-fibrotic through Ser77 phosphorylation-mediated ARNT/ARNT homodimer formation.

    Nyamsuren, Gunsmaa / Rapp, Gregor / Dihazi, Hassan / Zeisberg, Elisabeth M / Tampe, Desiree / Tampe, Björn / Zeisberg, Michael

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 24075

    Abstract: Aryl hydrocarbon receptor nuclear translocator (ARNT) mediates anti-fibrotic activity in kidney and liver through induction of ALK3-receptor expression and subsequently increased Smad1/5/8 signaling. While expression of ARNT can be pharmacologically ... ...

    Abstract Aryl hydrocarbon receptor nuclear translocator (ARNT) mediates anti-fibrotic activity in kidney and liver through induction of ALK3-receptor expression and subsequently increased Smad1/5/8 signaling. While expression of ARNT can be pharmacologically induced by sub-immunosuppressive doses of FK506 or by GPI1046, its anti-fibrotic activity is only realized when ARNT-ARNT homodimers form, as opposed to formation of ARNT-AHR or ARNT-HIF1α heterodimers. Mechanisms underlying ARNTs dimerization decision to specifically form ARNT-ARNT homodimers and possible cues to specifically induce ARNT homodimerization have been previously unknown. Here, we demonstrate that phosphorylation of the Ser77 residue is critical for ARNT-ARNT homodimer formation and stabilization. We further demonstrate that inhibition of PP2A phosphatase activity by LB100 enhances ARNT-ARNT homodimers both in vivo and in vitro (mouse tubular epithelial cells and human embryonic kidney cells). In murine models of kidney fibrosis, and also of liver fibrosis, combinations of FK506 or GPI1046 (to induce ARNT expression) with LB100 (to enhance ARNT homodimerization) elicit additive anti-fibrotic activities. Our study provides additional evidence for the anti-fibrotic activity of ARNT-ARNT homodimers and reveals Ser77 phosphorylation as a novel pharmacological target to realize the therapeutic potential of increased ARNT transactivation activity.
    MeSH term(s) Amino Acid Sequence ; Animals ; Aryl Hydrocarbon Receptor Nuclear Translocator/chemistry ; Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism ; Biomarkers ; Disease Models, Animal ; Disease Susceptibility ; Enzyme Inhibitors/pharmacology ; Fibrosis ; Kidney Diseases/etiology ; Kidney Diseases/metabolism ; Kidney Diseases/pathology ; Liver Cirrhosis/etiology ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/pathology ; Mice ; Phosphorylation/drug effects ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Phosphatase 2/antagonists & inhibitors ; Protein Phosphatase 2/metabolism ; Serine/metabolism ; Signal Transduction
    Chemical Substances Biomarkers ; Enzyme Inhibitors ; Aryl Hydrocarbon Receptor Nuclear Translocator (138391-32-9) ; Serine (452VLY9402) ; Protein Phosphatase 2 (EC 3.1.3.16)
    Language English
    Publishing date 2021-12-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-03523-1
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